title: Pathogenesis of acute stroke and the role of inflammasomes.
abstract: Inflammation is an innate immune response to infection or tissue damage that is designed to limit harm to the host, but contributes significantly to ischemic brain injury following stroke. The inflammatory response is initiated by the detection of acute damage via extracellular and intracellular pattern recognition receptors, which respond to conserved microbial structures, termed pathogen-associated molecular patterns or host-derived danger signals termed damage-associated molecular patterns. Multi-protein complexes known as inflammasomes (e.g. containing NLRP1, NLRP2, NLRP3, NLRP6, NLRP7, NLRP12, NLRC4, AIM2 and/or Pyrin), then process these signals to trigger an effector response. Briefly, signaling through NLRP1 and NLRP3 inflammasomes produces cleaved caspase-1, which cleaves both pro-IL-1β and pro-IL-18 into their biologically active mature pro-inflammatory cytokines that are released into the extracellular environment. This review will describe the molecular structure, cellular signaling pathways and current evidence for inflammasome activation following cerebral ischemia, and the potential for future treatments for stroke that may involve targeting inflammasome formation or its products in the ischemic brain.
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia.
authors.forename: David Yang-Wei
authors.initials: DY
authors.lastname: Fann
authors.forename: Seung-Yoon
authors.initials: SY
authors.lastname: Lee
authors.forename: Silvia
authors.initials: S
authors.lastname: Manzanero
authors.forename: Prasad
authors.initials: P
authors.lastname: Chunduri
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Sobey
authors.forename: Thiruma V
authors.initials: TV
authors.lastname: Arumugam
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D006801:Humans; D058847:Inflammasomes / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D020521:Stroke / Q000378:metabolism* / Q000473:pathology*
chemical_list: D058847:Inflammasomes
keywords: Caspase-1; Cytokines; Inflammasome; Ischemic stroke; Treatment